The major nuclear envelope targeting domain of LAP2 coincides with its lamin binding region but is distinct from its chromatin interaction domain.
LAP2 is an integral protein of the inner nuclear membrane which binds lamins and chromosomes and is suggested to have an important role in nuclear envelope organization. In a previous study we identified an internal 76-amino acid region of LAP2 which is required for stable targeting of the protein to the nuclear envelope. Here, we have mapped the lamin binding region of LAP2 and demonstrate that it coincides with this nuclear envelope targeting domain. In contrast, we found that the portion of LAP2 involved in binding to chromosomes resides in a separate region of the protein near its NH2 terminus. The minimal lamin binding region of LAP2 is capable of conferring stable nuclear envelope localization when attached to the transmembrane and partial lumenal domains of a protein that shows no nuclear envelope targeting activity. This directly supports the notion that a major mechanism for localization of integral membrane proteins at the inner nuclear membrane involves binding to lamins, which would constrain diffusion through the continuous nuclear envelope/endoplasmic reticulum membrane system.
Furukawa
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K
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Fritze
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CE
Gerace
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D001665:Binding Sites; D002463:Cell Membrane Permeability; D002843:Chromatin / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism; D004268:DNA-Binding Proteins; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells / Q000166:cytology; D006801:Humans; D034882:Lamins; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics; D017384:Sequence Deletion; D014162:Transfection / Q000235:genetics
D002843:Chromatin; D004268:DNA-Binding Proteins; D034882:Lamins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C093413:lamina-associated polypeptide 2